PUBLICATION

A UTP3-dependent nucleolar translocation pathway facilitates pre-rRNA 5'ETS processing

Authors
Bao, J., Su, B., Chen, Z., Sun, Z., Peng, J., Zhao, S.
ID
ZDB-PUB-240723-1
Date
2024
Source
Nucleic acids research   52(16): 9671-9694 (Journal)
Registered Authors
Peng, Jinrong
Keywords
none
Datasets
GEO:GSE244191, GEO:GSE262698
MeSH Terms
  • Animals
  • Cell Nucleolus*/genetics
  • Cell Nucleolus*/metabolism
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Nuclear Proteins/genetics
  • Nuclear Proteins/metabolism
  • RNA Precursors*/genetics
  • RNA Precursors*/metabolism
  • RNA Processing, Post-Transcriptional*
  • Zebrafish*/genetics
  • Zebrafish*/metabolism
(all 13)
PubMed
39036955 Full text @ Nucleic Acids Res.
Abstract
The ribosome small subunit (SSU) is assembled by the SSU processome which contains approximately 70 non-ribosomal protein factors. Whilst the biochemical mechanisms of the SSU processome in 18S rRNA processing and maturation have been extensively studied, how SSU processome components enter the nucleolus has yet to be systematically investigated. Here, in examining the nucleolar localization of 50 human SSU processome components, we found that UTP3, together with another 24 proteins, enter the nucleolus autonomously. For the remaining 25 proteins we found that UTP3/SAS10 assists the nucleolar localization of five proteins (MPP10, UTP25, EMG1 and the two UTP-B components UTP12 and UTP13), likely through its interaction with nuclear importin α. This 'ferrying' function of UTP3 was then confirmed as conserved in the zebrafish. We also found that knockdown of human UTP3 impairs cleavage at the A0-site while loss-of-function of either utp3/sas10 or utp13/tbl3 in zebrafish causes the accumulation of aberrantly processed 5'ETS products, which highlights the crucial role of UTP3 in mediating 5'ETS processing. Mechanistically, we found that UTP3 facilitates the degradation of processed 5'ETS by recruiting the RNA exosome component EXOSC10 to the nucleolus. These findings lay the groundwork for studying the mechanism of cytoplasm-to-nucleolus trafficking of SSU processome components.
Genes / Markers
Figures
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
zju9
    Indel
    1 - 1 of 1
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    Human Disease / Model
    No data available
    Sequence Targeting Reagents
    Target Reagent Reagent Type
    tbl3CRISPR1-tbl3CRISPR
    1 - 1 of 1
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    Fish
    No data available
    Antibodies
    No data available
    Orthology
    No data available
    Engineered Foreign Genes
    No data available
    Mapping
    No data available